The present invention relates to a 2-aminopropane-1,3-diol compound useful for pharmaceuticals, particularly immunosuppressants, a pharmaceutical use thereof and a synthetic intermediate therefor.
WO94/08943 discloses 2-aminopropane-1,3-diol compounds including 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride useful as a suppressant of rejection in organ or bone marrow transplantation, or as a therapeutic agent of various autoimmune diseases such as psoriasis, Beh.cedilla.et's disease and the like, and rheumatic diseases. WO96/06068 discloses a benzene compound useful as a suppressant of rejection in organ or bone marrow transplantation or as a therapeutic agent of various autoimmune diseases such as psoriasis, Beh.cedilla.et's disease and the like, and rheumatic diseases.
J. Org. Chem., vol. 25, p2057-2059 (1960) teaches 2-methylamino-2-(phenylmethyl or phenylmethyl substituted by 2-methyl, 3-methyl, 4-methyl, 4-methoxy or 4-hydroxy)propane-1,3-diol. In U.S. Pat. No. 3,660,488, 2amino-2-(p-chlorobenzyl)propane-1,3-diol as an anti-radiation drug is disclosed.
The object of the present invention is to provide a more effective and highly safe compound as a suppressant of rejection in organ or bone marrow transplantation or as a therapeutic agent of autoimmune diseases such as atopic dermatitis, psoriasis, articular rheumatism and Beh.cedilla.et's disease, a pharmaceutical comprising the said compound, and a synthetic key compound of the said compound.
The present inventors have made intensive studies in order to achieve the above-mentioned object, and found that, of the 2-aminopropane-1,3-diol compounds represented by the general formula disclosed in WO94/08943 ##STR2##
a compound wherein, at the substituent R of this compound, a p-phenylene group in the carbon chain and a phenyl group at the end of the carbon chain are substituted and, in the carbon chain between the said p-phenylene group and the phenyl group, the carbon at the .beta.-position of the p-phenylene group is substituted by a carbonyl group (these compounds are not disclosed concretely in the said official gazette) possesses less toxicity, high safety and superior immunosuppressive action, which resulted in the completion of the present invention.